1. Field of the Invention
The present invention relates to a method and composition for treating cancer. More specifically, the present invention relates to the use of lipophilic synthetic derivatives of ascorbic acid, e.g., Ascorbyl stearate and Ascorbyl palmitate in treating cancer cells.
2. Description of Related Art
Pancreatic cancer of ductal type (DAP) is the leading cause of cancer death world wide1. This highly aggressive tumor affects patients usually older than 50 years, and its incidence is increasing, particularly in women. This tumor has short median survival, and high mortality rate. DAP""s present late in their development and are unresectable in 30% of cases. The American Cancer Society estimates that there will be 28,600 new cases of pancreatic cancer in 1999 in USA, with 28,600 estimated pancreatic cancer deaths in the same year. These observations attest the inefficacy of current treatment modalities for this form of human cancer, and the limited knowledge of the pathogenic mechanisms leading to pancreatic cancer. These unsatisfactory results warrant a search for alternative treatments.
Additionally, colorectal cancer is a common neoplasm second only to lung cancer as the leading cause of death due to cancer in the United States. Advanced colon cancer is refractory to most chemotherapeutic agents. 5-Fluorouracil (5 FU) remains the most effective single agent with a response rate of 10-20% further showing the need for alternative treatments.
In vitro and in vivo studies of ascorbyl esters as antiproliferative compounds showed with preliminary results. For example, Ascorbyl esters have been found to inhibit cell proliferation and DNA synthesis of breast, skin, and brain tumors. These compounds are lipophilic, non-toxic, and can easily enter the intracellular compartment. However, there has been no study establishing any apoptotic activity for these ascorbyl esters.
Aberrant expression of IGF1 and IGF1-R has recently been reported in several human pancreatic cancer cell lines and in cancer cell lines and in cancerous human pancreatic tissues. It seems that the autocrine interaction between the IGF1-R and its ligand regulates both autonomous, anchorage-independent growth, and tumorigenicity of pancreatic carcinoma cells9-10. It would therefore be useful to develop a method and composition which regulates the expression of IGF1 and IGF1-R, thus causing apoptosis of these cancer cell lines.
L-Ascorbyl 6-palmitate (As-P), a synthetic lipophilic derivative of ascorbic acid, is widely used as a food additive to retard the development of oxidative rancidity in high-fat foods. Other useful functions as As-P in foods are: preventing nitrosamine formation while bacon is fried, conditioning yeasted doughs, lengthening shelf-life of bread and emulsifying carotinoid pigments. Besides its antioxidant activity, a few studies suggested that As-P may also possess antitumor activity in glioma cells.
It would therefore be useful to determine a method and composition for use in cancers. It would also be useful to develop a method and composition with an increased response rate for the treatment of cancer.
According to the present invention, there is provided a method of treating cancer by treating the cancer cells with a lipophilic synthetic derivative of ascorbic acid. Also provided is a method of inhibiting the Ras pathway by administering a lipophilic derivative of ascorbic acid. A method of inducing apoptosis in cancer cells is also provided by treating cancer cells with a lipophilic derivative of Asc-S. A pharmaceutical composition for the treatment of cancer including pharmaceutically acceptable carrier for Asc-S is also provided.